Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
An age related decline in explicit forms of memory has been consistently observed in various species including human, non-human primates and rodents (Gage et al., 1989; Barnes, 1994). In experimental animals, including monkeys, rats, and mice, age is also accompanied by a loss of explicit forms of learning and memory evident in spatial tasks (deToledo-Morell et al., 1988; Aggleton et al., 1989; Fischer et al., 1989). The search for central loci in the brain responsible for these changes in explicit memory and. defining the cellular and molecular mechanisms that lead to such changes is the focus of many researchers. Among the many model systems used to study this phenomena, the hippocampus and its related structures have been the most intensively studied in aging (Landfield, 1988; Barnes, 1994). The hippocampus and its related temporal lobe structures are important for explicit forms of memory (Squire & Zola-Moran, 1991; Squire, 1992). Interestingly, severe cases of explicit memory impairment and loss are seen in patients with amnesia or Alzheimer's disease which are known to have hippocampal disruptions. Hippocampal long-term potentiation (LTP) is a well established cellular model for memory storage (Bliss & Collingridge, 1993).